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Biomedical subjects

M D Miller

Publications and source records attributed to M D Miller.

At least 91 records · Page 5Linked to original sources

Intracorporeal lithotripsy with the Alexandrite laser.

BACKGROUND AND OBJECTIVE: The objective of this study was to evaluate clinical use of an Alexandrite laser lithotripter for intracorporeal lithotripsy of urinary calculi. STUDY DESIGN/MATERIALS AND METHODS: We prospectively evaluated a flash lamp pumped, Q-switched Alexandrite solid-state laser for use in conjunction with ureteroscopy (30 cases) or percutaneous nephrolithotripsy (2 cases). The laser operates at a wavelength of 755 nm in a pulsed mode with pulses of 150-800 ns duration at energy settings of 30-80 mJ. RESULTS: The fragmentation rate with the Alexandrite laser alone was 50% (16/32). Failure of the laser was due to equipment malfunction or technical problems in 11 cases and inability to fragment the stone in 5. All cases of failed Alexandrite laser lithotripsy were successfully salvaged with alternative modalities of endoscopic stone destruction and removal. One intraoperative complication, a ureteral perforation, occurred; however, no long-term sequelae related to laser use was documented. CONCLUSION: Clinical results with the Alexandrite laser appear to be inferior to those reported with Alternative laser systems and other forms of intracorporeal lithotripsy. Whereas some of the inadequacies we have noted may be addressed in the future by modifications in the unit and delivery systems, we would not recommend this device for intracorporeal lithotripsy of urinary calculi in its current form.

Adult↗

Office procedures. Education, training, and proficiency of procedural skills.

Clinical competence exists when a practitioner has sufficient knowledge and skill such that a procedure can be performed to obtain intended outcomes without harm to the patient. Practitioners who want to be competent in performing clinical procedures should examine how the procedures are relevant to their practice, place the procedures in a familiar context, learn what outcomes are expected, and practice self-evaluation. Competence has several components, including knowledge, clinical decision making, judgment, technical skills, attitudes, professional habits, and interpersonal skills. Each of these must be mastered using a variety of sources of information and skill acquisition.

Clinical Competence↗

Cruciate ligament graft intra-articular distances.

Although the length of the anterior and posterior cruciate ligaments have been well characterized in the literature, we are not aware of any studies of the actual length of grafts used in reconstruction of these ligaments. We dissected and measured these distances for 18 cadaver knees of varying size and sex. The precise location of ideal guide pin placement was located based on current recommendations, and the intra-articular graft length was measured with a micrometer by two separate observers. We found that the average intra-articular graft length for the anterior cruciate ligament is 23.56 mm (SD, 0.98 mm), the posterior cruciate ligament is 30.72 mm (SD, 2.61 mm) and the patella tendon graft intertendinous distance is 43.33 mm (SD, 4.21 mm) We conclude that the intra-articular distance for cruciate ligament grafts is less than published values for the ligaments themselves, and that the patella tendon graft is of adequate length to be used for reconstruction of these ligaments.

Anterior Cruciate Ligament↗

Arthroscopically assisted reduction and fixation of an adult Tillaux fracture of the ankle.

We describe the first report of arthroscopically-assisted reduction and fixation of an adult Tillaux fracture. Anatomic reduction of the fracture was possible with arthroscopic visualization. Adjunctive use of the arthroscope for accurate reduction of intraarticular fractures, which has been successful in the management of distal radius and tibial plateau fractures, can also be used for adult Tillaux fractures of the ankle.

Ankle Injuries↗

Using relative value units to measure faculty clinical productivity.

The objective of this project was to compare faculty productivity in teaching and nonteaching clinical settings. We hypothesized that teaching activity would have no impact on productivity. A mixed model, repeated measures analysis of variance was used to analyze average relative value units (RVUs) billed and to test for differences between clinics. Data were drawn from 4,956 clinical encounters made within a student, resident, and faculty clinic. Average RVUs per visit were similar in the three settings. Resident supervision increased faculty productivity, while student supervision had no impact on billed RVUs. Thus, RVUs can be used as a measure of faculty clinical productivity in different settings in an academic medical center. Precepting students does not appear to affect clinical productivity.

Efficiency, Organizational↗

Tethering human immunodeficiency virus type 1 preintegration complexes to target DNA promotes integration at nearby sites.

Integration of retroviral cDNA in vivo is normally not sequence specific with respect to the integration target DNA. We have been investigating methods for directing the integration of retroviral DNA to predetermined sites, with the dual goal of understanding potential mechanisms governing normal site selection and developing possible methods for gene therapy. To this end, we have fused retroviral integrase enzymes to sequence-specific DNA-binding domains and investigated target site selection by the resulting proteins. In a previous study, we purified and analyzed a fusion protein composed of human immunodeficiency virus integrase linked to the DNA-binding domain of lambda repressor. This fusion could direct selective integration in vitro into target DNA containing lambda repressor binding sites. Here we investigate the properties of a fusion integrase in the context of a human immunodeficiency virus provirus. We used a fusion of integrase to the DNA binding domain of the zinc finger protein zif268 (IN-zif). Initially we found that the fusion was highly detrimental to replication as measured by the multinuclear activation of a galactosidase indicator (MAGI) assay for infected centers. However, we found that viruses containing mixtures of wild-type integrase and IN-zif were infectious. We prepared preintegration complexes from cells infected with these viruses and found that such complexes directed increased integration near zif268 recognition sites.

Cell Line, Transformed↗

Human immunodeficiency virus type 1 preintegration complexes: studies of organization and composition.

We have investigated the organization and function of human immunodeficiency virus type 1 (HIV-1) preintegration complexes (PICs), the large nucleoprotein particles that carry out cDNA integration in vivo. PICs can be isolated from HIV-1-infected cells, and such particles are capable of carrying out integration reactions in vitro. We find that although the PICs are large, the cDNA must be condensed to fit into the measured volume. The ends of the cDNA are probably linked by a protein bridge, since coordinated joining of the two ends is not disrupted by cleaving the cDNA internally with a restriction enzyme. cDNA ends in PICs were protected from digestion by added exonucleases, probably due to binding of proteins. The intervening cDNA, in contrast, was susceptible to attack by endonucleases. Previous work has established that the virus-encoded integrase protein is present in PICs, and we have reported recently that the host protein HMG I(Y) is also present. Here we report that the viral matrix and reverse transcriptase (RT) proteins also cofractionated with PICs through several steps whereas capsid and nucleocapsid proteins dissociated. These data support a model of PIC organization in which the cDNA is condensed in a partially disassembled remnant of the viral core, with proteins tightly associated at the apposed cDNA ends but loosely associated with the intervening cDNA. In characterizing the structure of the cDNA ends, we found that the U5 DNA ends created by RT were ragged, probably due to the terminal transferase activity of RT. Only molecules correctly cleaved by integrase protein at the 3' ends were competent to integrate, suggesting that one role for terminal cleavage by integrase may be to create a defined end at otherwise heterogeneous cDNA termini.

DNA, Viral↗

Bereavement and late-life depression: grief and its complications in the elderly.

Spousal bereavement is a common event in later life and, not infrequently, an important cause of psychiatric and medical morbidity. Depression (along with suicide), anxiety, substance abuse, and symptoms of "complicated" grief are among the more important psychiatric sequelae of spousal bereavement. They may represent, in part, forms of abnormal reaction to the stress of loss and the challenges of adaption to becoming widowed. This paper summarizes current knowledge about the clinical phenomenology of the psychiatric sequelae to late-life attachment bereavement, some of the hypothesized antecedents of abnormal stress response to bereavement, psychobiologic correlates of bereavement-related depression, and the long-term course (including preliminary evidence on response to treatment with psychotherapy and antidepressant medication).

Aged↗

Strength of fixation with transosseous sutures in rotator cuff repair.

The effect of various configurations of placement of transosseous sutures on the immediate strength of fixation was studied in forty-five fresh-frozen humeri from cadavera of older individuals (mean age at the time of death, sixty-three years). The ultimate strength (the strength to failure) was significantly greater (p < 0.05) when the sutures were placed at sites more distal to the tip of the greater tuberosity or when the sutures were tied over a wider bone bridge. Cortical augmentation with use of a plastic button through which the transosseous sutures were tied increased the ultimate strength approximately 1.9-fold. The increase in the ultimate strength of the transosseous repair corresponded significantly with the increasing mean thickness of the cortical bone as the sutures were placed more distally along the lateral aspect of the humerus. We concluded that the strength of the fixation of a rotator cuff repair can be increased by placing the transosseous sutures at least ten millimeters distal to the tip of the greater tuberosity and by tying them over a bone bridge that is at least ten millimeters wide. When bone is very osteoporotic, cortical augmentation with a readily available plastic button strengthens the repair.

Aged↗

The efficacy of orthotics for anterior knee pain in military trainees. A preliminary report.

This study was undertaken to determine if commonly used orthotics (Palumbo "Dynamic Patellar Brace" [DynOrthotics, Vienna, Virginia] and the Cho-Pat Knee Strap [Cho-Pat Inc, Hainesport, New Jersey]) are helpful in the management of anterior knee pain in an active population who are unable to significantly modify their activity due to basic training requirements. In a prospective, randomized study, 59 Air Force Academy basic cadets who presented with anterior knee pain during the initial phases of basic cadet training, were placed into one of the three treatment groups. Group A was assigned no brace, group B was issued a Palumbo "Dynamic Patellar Brace," and group C was issued a Cho-Pat Knee Strap. All patients were started on physical therapy with "closed chain" rehabilitation and given nonsteroidal anti-inflammatory medications. Patients then underwent weekly follow-up with serial examinations and completion of a visual analog pain/motivation questionnaire. At the completion of training (6 to 8 weeks after study initiation), all charts were collected and statistically analyzed with analysis of variance (ANOVA). Eight patients were removed from the study group because of insufficient follow-up or failure to complete training (correlated with low motivation scales). There was no significant difference between the groups regarding change in pain throughout the study. The only statistically significant item was the proportion of females presenting with anterior knee pain (2.7% versus 1.4% incidence). Two patients voluntarily separated (disenrolled) due to incapacitating anterior knee pain at the completion of the study. Both of these patients were assigned to the Palumbo group. Despite manufacturer claims, these two orthotics do not appear to be effective in controlling anterior knee pain in this basic trainee populations.

Analysis of Variance↗

The posttreatment illness course of depression in bereaved elders. High relapse/recurrence rates.

Losing close attachments through death in late life is common and can lead to depression. Previous work has shown the clinical benefits of treating these depressions. This article describes the 2-year course of 53 elderly subjects with bereavement-related depression after responding to various treatments. Forty-six patients experienced a full response to acute treatment, but 36% experienced relapse or recurrence. This finding suggests that the treatment response in depressed bereaved older patients is more brittle than expected.

Aged↗

Using interpersonal psychotherapy (IPT) in a combined psychotherapy/medication research protocol with depressed elders. A descriptive report with case vignettes.

One hundred eighty subjects at least 60 years of age with recurrent unipolar major depression were recruited to participate in a depression treatment protocol. All patients received drug therapy with nortriptyline (NT) and interpersonal psychotherapy (IPT) with an experienced clinician. Acutely, 81% of subjects showed a full response to combined treatment. In the initial 127 subjects, the most common problem areas in therapy were role transition (41%), interpersonal disputes (34.5%), and grief (23%). Case vignettes are presented and discussed. The combination of IPT and NT showed a powerful antidepressant effect. IPT was readily adaptable to the needs of depressed elders.

Aged↗

Target-sequence preferences of HIV-1 integration complexes in vitro.

Integration of reverse transcribed retroviral cDNA is not restricted to particular host DNA sequences. However, the frequency of integration into a particular phosphodiester bond is influenced by the local sequence. Here we examine the target-sequence preferences of purified HIV integrase and viral nucleoprotein complexes (preintegration complexes) isolated from freshly infected cells. We find that the three-base sequence including the integration site is not the major factor determining the frequency of integration, since identical triplets embedded in different sequences are used with very different efficiencies. However, there is a statistically significant bias against integration upstream of a pyrimidine nucleotide. The target-sequence preferences of purified integrase and preintegration complexes are very different. Strong integration sites on opposite DNA strands occur in pairs separated by five residues when preintegration complexes are used but not with purified integrase. These studies highlight the difference between the two sources of HIV integration activity and may provide the basis for a simple assay for the correct assembly of viral nucleoprotein complexes.

Binding Sites↗

Identification of the Serratia endonuclease dimer: structural basis and implications for catalysis.

The Serratia endonuclease is an extracellularly secreted enzyme capable of cleaving both single- and double-stranded forms of DNA and RNA. It is the first member of a large class of related and usually dimeric endonucleases for which a structure is known. Using X-ray crystallography, the structure of monomer of this enzyme was reported by us previously (Miller MD et al., 1994, Nature Struct Biol 1:461-468). We now confirm the dimeric nature of this enzyme through light-scattering experiments and identify the physiologic dimer interface through crystal packing analysis. This dimerization occurs through an isologous twofold interaction localized to the carboxy-terminal subdomain of the enzyme. The dimer is a prolate ellipsoid with dimensions 30 A x 35 A x 90 A. The dimer interface is flat and contains four salt links, several hydrogen bonds, and nonpolar interactions. Buried water is prominent in this interface and it includes an unusual "cubic" water cluster. The position of the two active sites in the dimer suggests that they can act independently in their cleavage of DNA, but have a geometrical advantage in attacking substrate relative to the monomer.

Biopolymers↗